The Imaging Core of the Cleveland Clinic Lerner Research Institute (LRI) and a group of seventeen NIH-funded investigators request funds to purchase a transmission electron microscope (TEM) - specifically the FEI Tecnai Spirit BioTwin. The Imaging Core was established sixteen years ago to provide leading-edge microscopy equipment and expertise for the Cleveland Clinic research community. The Core has a 21-year-old FEI CM12 TEM, used by 58 registered investigators from 18 departments. This instrument has served our researchers well, but has required more frequent service calls and was, in fact, declared obsolete by the manufacturer at the end of last year (and is no longer eligible for a full service contract). Besides the problems caused for research projects by equipment downtime, our film-based TEM is slow, unreliable, and expensive. The instrument we are requesting herein will provide a dependable resource for all of the basic capabilities of the existing TEM, but will also offer digital imaging. Although our Core provides a great array of top-notch microscopes for biomedical imaging, there are many NIH-funded research goals that can only be pursued with electron microscopy, making it essential for a facility such as ours to have an up-to-date instrument. Knowledge obtained from the projects highlighted here will hopefully lead to better modes of prevention and treatment for conditions such as inflammatory diseases, pelvic floor disorders, pulmonary arterial hypertension, cancer, kidney failure, Alzheimer's disease, atherosclerosis, atrial fibrillation, and birth defects. Placing the system in the Imaging Core - with its centrality in a significant research facility - will not only maximize its benefits for a variety of health-related investigations, but will assure its management by a skilled staff. Dr. Judith Drazba, LRI Imaging Core Director, has over twenty seven years electron microscopy experience, sixteen of them running this facility. A full-time EM technician, also with long experience, oversees the operation of the TEM and provides complete sample preparation. A Core manager also assists with user services and equipment troubleshooting and maintenance. Finally, the Lerner Research Institute which has a long history of strong support for centralized facilities continues its commitment to the Imaging Core by providing funds for salary support, service contracts, and infrastructure. PUBLIC HEALTH RELEVANCE: Use of the electron microscope proposed in this grant will give researchers the ability to produce highly magnified images of cells and tissues to see details on a much smaller scale than with light microscopes. Observing the ultrastructure of these samples leads to a better understanding of how they are organized and how they operate. With the knowledge obtained from use of this instrument, our investigators hope to discover better modes of prevention and treatment for conditions such as inflammatory diseases, pelvic floor disorders, pulmonary arterial hypertension, cancer, kidney failure, Alzheimer's disease, atherosclerosis, atrial fibrillation, and birth defects.